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1.
J Enzyme Inhib Med Chem ; 39(1): 2290912, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38083866

RESUMO

Targeting Heat shock protein 90 (HSP90) C-terminus is an important strategy to develop HSP90 inhibitors without inducing heat shock response. The development of C-terminal inhibitors, however, is hampered by a lack of understanding regarding the interaction between the HSP90 C-terminus and the present inhibitors. We collected seven classical and structurally diverse HSP90 C-terminal inhibitors and constructed a ligand-based pharmacophore model. The subsequent virtual screening and structural optimisation led to the identification of 2-heteroarylthio-N-arylacetamides as novel HSP90 C-terminal inhibitors. 9 and 27 exhibited strong antitumour activity in vitro by inhibiting proliferation and inducing apoptosis in multiple cancer cell lines. These compounds disrupted the interaction between HSP90 C-terminus and peptidylprolyl isomerase D, exerting a stronger inhibitory effect than novobiocin. 27 significantly induced the degradation of HSP90 clients without triggering heat shock response. In an in vivo study using 4T1 mice breast cancer models, 9 showed a potent antitumour effect without obvious toxicity.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Animais , Camundongos , Farmacóforo , Ligantes , Antineoplásicos/farmacologia , Antineoplásicos/química , Proteínas de Choque Térmico HSP90 , Linhagem Celular Tumoral , Proliferação de Células
2.
Oral Dis ; 29(5): 2006-2011, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35426211

RESUMO

PURPOSE: To obtain the relative volume by measuring the tongue volume and the lesion volume, and further explore its relationship with the prognosis of patients, hoping to supplement the TNM staging with a new index. METHODS: ITK-SANP software was used to outline the patients' MRI. After MRI reconstruction and measurement, slicer software was used to estimate tumor volume. RESULTS: A total of 64 patients with tongue cancer who met the inclusion criteria were included in the study. The estimated tumor volume after MRI reconstruction revealed a significant and robust correlation with tumor stage (p < 0.05, Rs = 0.6207) and a substantial and medium correlation with early lymph node metastasis (p < 0.05, Rs = 0.4873). CONCLUSIONS: We classified tongue cancer into three grades based on tumor volume (Stage I, tumors smaller than 1500 mm³; Stage II, tumors 1500-9000 mm³; and Stage III, tumors larger than 9000 mm³), and such grading could be used as a reference for tumor staging, lymph node metastasis, and patient prognosis to a certain extent.


Assuntos
Neoplasias da Língua , Humanos , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Estudos Retrospectivos , Prognóstico , Estadiamento de Neoplasias , Imageamento por Ressonância Magnética , Língua , Linfonodos/patologia
3.
J Enzyme Inhib Med Chem ; 37(1): 2551-2565, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36120957

RESUMO

The molecular chaperone HSP90 plays an essential role in cancer occurrence and development. Therefore, it is an important target for the development of anticancer drugs. 1,3-Dibenzyl-2-aryl imidazolidine (8) is a previously reported inhibitor of HSP90; however, its anticancer activity is poor. In this work, chemical modification of 8 led to the discovery of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as two types of novel HSP90 N-terminal inhibitors. 16l and 22k exhibited antiproliferative activity against multiple breast cancer cell lines with IC50 values at the low micromolar level. 16l and 22k induced significant degradation of the client proteins AKT and ERK and a lower level of the heat shock response in comparison with tanespimycin (17-AAG). 22k exhibited a strong affinity for the HSP90α N-terminus with an IC50 value of 0.21 µM. A molecular docking study revealed that 16l and 22k successfully bind to the geldanamycin binding site at the N-terminus of HSP90α.


Assuntos
Antineoplásicos , Imidazolidinas , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzoquinonas , Proteínas de Choque Térmico HSP90 , Humanos , Lactamas Macrocíclicas , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-akt
4.
Hum Genomics ; 14(1): 24, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522293

RESUMO

BACKGROUND: Colon adenocarcinoma (COAD) is one of the common gastrointestinal malignant diseases, with high mortality rate and poor prognosis due to delayed diagnosis. This study aimed to construct a prognostic prediction model for patients with colon adenocarcinoma (COAD) recurrence. METHODS: Differently expressed RNAs (DERs) between recurrence and non-recurrence COAD samples were identified based on expression profile data from the NCBI Gene Expression Omnibus (GEO) repository and The Cancer Genome Atlas (TCGA) database. Then, recurrent COAD discriminating classifier was established using SMV-RFE algorithm, and receiver operating characteristic curve was used to assess the predictive power of classifier. Furthermore, the prognostic prediction model was constructed based on univariate and multivariate Cox regression analysis, and Kaplan-Meier survival curve analysis was used to estimate this model. Furthermore, the co-expression network of DElncRNAs and DEmRNAs was constructed followed by GO and KEGG pathway enrichment analysis. RESULTS: A total of 54 optimized signature DElncRNAs were screened and SMV classifier was constructed, which presented a high accuracy to distinguish recurrence and non-recurrence COAD samples. Furthermore, six independent prognostic lncRNAs signatures (LINC00852, ZNF667-AS1, FOXP1-IT1, LINC01560, TAF1A-AS1, and LINC00174) in COAD patients with recurrence were screened, and the prognostic prediction model for recurrent COAD was constructed, which possessed a relative satisfying predicted ability both in the training dataset and validation dataset. Furthermore, the DEmRNAs in the co-expression network were mainly enriched in glycan biosynthesis, cardiac muscle contraction, and colorectal cancer. CONCLUSIONS: Our study revealed that six lncRNA signatures acted as an independent prognostic biomarker for patients with COAD recurrence.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Modelos Estatísticos , Recidiva Local de Neoplasia/patologia , RNA Longo não Codificante/genética , Adenocarcinoma/genética , Idoso , Neoplasias do Colo/genética , Feminino , Seguimentos , Redes Reguladoras de Genes , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Prognóstico , Taxa de Sobrevida
5.
Mol Carcinog ; 59(12): 1323-1342, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128289

RESUMO

This study aimed to investigate the role of circ0106714-miR-942-5p-discs large homolog 2 (DLG2), a novel interactome, in colorectal cancer (CRC). Circ0106714 was found to be the most significantly downregulated circular RNA in CRC using a bioinformatics method, and we researched whether the ability of circ0106714 to sponge miR-942-5p and release DLG2 could affect CRC development via Hippo-YES-associated protein (YAP) signaling. We first employed qRT-PCR and immunoblotting to detect messenger RNA (mRNA) and protein expression, respectively. Live imaging of mice tumor xenografts was then conducted to study the effect of circ0106714 on tumor progression in vivo. Reporter gene assays were subsequently conducted to verify the predicted targeting relationship between circ0106714, miR-942-5p, and DLG2 mRNA in SW480 and HCT116 cell lines. As well as using flow cytometry for both apoptosis and cell cycle profile analyses, CCK-8 and clone foci formation assays were performed to assess cell survival. Wound healing assay and transwell invasion assay were later carried out to evaluate the migration and invasion of the cell lines. Findings revealed that circ0106714 and DLG2 were significantly downregulated, while miR-942-5p was significantly upregulated in human CRC tissues and cell lines. However, circ0106714 upregulation significantly suppressed tumor progression in vivo and inhibited the malignancy phenotypes of tumor cells in vitro by targeting miR-942-5p. Also discovered in this research was that miR-942-5p could directly target DLG2 mRNA, thus enhancing the malignancy phenotypes of CRC cells. We even found that DLG2 overexpression resulted in enhanced phosphorylation of YAP, a critical downstream effector of DLG2. This downstream effector was demonstrated to have a tumor-suppressive capacity in CRC cell lines. In sum, circ0106714 could suppress CRC by sponging miR-942-5p and releasing DLG2, thus promoting YAP phosphorylation.


Assuntos
Neoplasias Colorretais/patologia , Guanilato Quinases/genética , MicroRNAs/genética , RNA Circular/genética , Proteínas Supressoras de Tumor/genética , Idoso , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Guanilato Quinases/metabolismo , Células HCT116 , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Transplante de Neoplasias , Fosforilação , Transdução de Sinais , Análise de Sobrevida , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
6.
Cancer Cell Int ; 20: 303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32675943

RESUMO

BACKGROUND: Gastric cancer (GC) is the leading cause of death worldwide and is closely related to metastasis. MRTF-A is one of the most well-characterized genetic markers in cancer. However, the mechanism whereby MRTF-A mediate gastric cancer (GC) tumorigenesis is not fully clear. Increasing evidence has confirmed that miRNA dysregulation is involved in MRTF-A-mediated tumorigenesis, supporting their potential as therapeutic targets for cancer. Although miR-155 has been reported as an upregulated miRNA, the interplay between miR-155 and MRTF-A-mediated gastric cancer progression remain largely elusive. METHODS: Real-time PCR was performed to determine miR-155 expression after transfected with MRTF-A encoding plasmids and siRNA. Potential target genes were identified by Western blot and luciferase reporter assay. Chip assay was proved that MRTF-A binds in the promoter region of miR-155. Transwell assay and Scratch-healing migration assay was used to investigate the role of MRTF-A and SOX1 in gastric cancer cell migration and invasion. RESULTS: MRTF-A can interact with the miR-155 promoter to promote histone acetylation and RNA polymerase II recruitment via the Wnt-ß-catenin pathway. miR-155 promotes gastric cancer cell migration by suppressing SOX1 expressiom by targeting its 3'UTR in vitro and in vivo. MRTF-A inhibited the inhibitory effects of SOX1 on gastric cancer cell migration by promoting the express -ion of miR-155. CONCLUSION: Our data therefore provide important and novel insights into how the MRTF-A/miR-155/SOX1 pathway mediates migration and invasion in GC.

7.
Med Sci Monit ; 25: 9435-9445, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31823961

RESUMO

BACKGROUND The RNA-seq FPKM data of 331 colorectal adenocarcinoma samples in The Cancer Genome Atlas database with matching clinical data were analyzed in order to reveal the prognostic value of m6A RNA methylation regulators in colon adenocarcinoma. MATERIAL AND METHODS The expression of 13 m6A RNA methylated regulators in samples were analyzed. The samples were classified into Cluster I and II by consistent clustering. The gene distribution was analyzed by principal component analysis. Further functional analysis of selected m6A RNA genes was performed and potential risk characteristics was developed using Lasso Cox regression algorithm. Using minimum criteria, the risk coefficients of YTHDF1 and HNRNPC were detected for Cluster II. Patients were divided into high-risk and low-risk subgroups based on the risk characteristics. The clinical data were analyzed by univariate and multivariate Cox regression analysis. RESULTS Expression of the detected m6A RNA methylated regulators except YTHDC2 in tumors were significantly different from their adjacent mucosa. Among them, only ALKBH5 and METTL4 were downregulated in tumors. The gene distribution between the 2 subgroups were different. The expression of m6A RNA methylation regulators including YTHDF1, HNRNPC, YTHDC2, YTHDC1, ZC3H13, and RBM15 were different between the 2 groups (P<0.05). The prognostic characteristics between the high-risk and low-risk groups were significant different (P<0.05), which had a good predictive significance of prognosis area under the curve (AUC)=0.62). Risk scores were less than 0.05, suggesting risk score was an independent prognostic factor for colon adenocarcinoma. CONCLUSIONS m6A RNA methylation regulators YTHDF1 and HNRNPC can be used as prognostic factors of colon cancer, which has potential value for colon cancer treatment.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Metiltransferases/metabolismo , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenosina/metabolismo , Adenosina Trifosfatases/metabolismo , Algoritmos , Análise por Conglomerados , Colo/metabolismo , Neoplasias do Colo/enzimologia , Neoplasias do Colo/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Humanos , Metilação , Metiltransferases/genética , Análise Multivariada , Prognóstico , RNA/genética , RNA Helicases/genética , Proteínas de Ligação a RNA/genética , tRNA Metiltransferases/metabolismo
8.
Arch Pharm Res ; 47(5): 442-464, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38632167

RESUMO

The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer.


Assuntos
Proteínas de Choque Térmico HSP90 , Neoplasias , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada
9.
Heliyon ; 10(11): e31920, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38882383

RESUMO

This study conducted experimental analyses on a 280 Ah single lithium iron phosphate battery using an independently constructed experimental platform to assess the efficacy of compressed nitrogen foam in extinguishing lithium-ion battery fires. Based on theoretical analysis, the fire-extinguishing effects of compressed nitrogen foam at different outlet pressures from foam mixture tanks were analyzed, examining factors such as battery surface temperature, flame temperature, and thermal weight loss. The results indicate that the compressed nitrogen foam can extinguish the open flame of the battery in 14 s at 0.7 MPa, with the battery's surface temperature dropping by approximately 11 % before and after the application of the extinguishing agent. Compared with other commonly used extinguishing agents, the compressed nitrogen foam demonstrates superior extinguishing efficiency, but its cooling efficiency is somewhat lower. At pressures ranging from 0.4 to 0.6 MPa, the foam displays prolonged drainage time and sustained cooling effects, rendering it more suitable for lithium-ion battery fire scenarios. To address the issue of reduced cooling performance during later stages of fire suppression by compressed nitrogen foam, an intermittent injection approach has been proposed to effectively preserve its cooling efficacy.

10.
Cell Death Discov ; 10(1): 200, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684668

RESUMO

Receptor-interacting protein kinase 3 (RIPK3), a member of the receptor-interacting protein kinase (RIPK) family with serine/threonine protein kinase activity, interacts with RIPK1 to generate necrosomes, which trigger caspase-independent programmed necrosis. As a vital component of necrosomes, RIPK3 plays an indispensable role in necroptosis, which is crucial for human life and health. In addition, RIPK3 participates in the pathological process of several infections, aseptic inflammatory diseases, and tumors (including tumor-promoting and -suppressive activities) by regulating autophagy, cell proliferation, and the metabolism and production of chemokines/cytokines. This review summarizes the recent research progress of the regulators of the RIPK3 signaling pathway and discusses the potential role of RIPK3/necroptosis in the aetiopathogenesis of various diseases. An in-depth understanding of the mechanisms and functions of RIPK3 may facilitate the development of novel therapeutic strategies.

11.
Food Chem X ; 22: 101264, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38468635

RESUMO

Workshop with different fermentation years plays an essential role in the yield and quality of Baijiu. In actual production, the quality of base Baijiu in newly built workshop is inferior to the older one. In this study, the microbiota of workshop environment and fermentation process from two workshops namely N (ferment 2 years) and O (ferment 20 years) and flavor compounds were studied during Xiasha round. Results showed workshop O accumulated more environmental microorganisms and fungi including P. kudriavzevii, Wickerhamomyces anomalus and Saccharomyces sp mainly came from ground. Yeasts including Pichia, Cyberlindnera, Wickerhamomyces and Candida were responsible for flavor substances formation in O while Saccharopolyspora was in N. This study for the first time explored the reasons for the brewing differences among N and O workshop from perspectives of workshop environment, microbial community and flavor substances, providing new ideas for guiding production as well as improvement of Baijiu quality.

12.
ACS Omega ; 8(14): 12968-12979, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37065020

RESUMO

Due to the complicacy of asphalt fumes, the analytical methods for investigating volatile organic compounds (VOCs) are very limited. In this study, a direct and real-time analysis method based on carbon fiber ionization mass spectrometry (CFI-MS), an ambient mass spectrometric technique, was established and successfully applied in the analysis of asphalt VOCs. The asphalt VOCs can be directly detected in the open atmosphere without the collection step of asphalt fumes, and the mass spectra of one asphalt sample can be obtained in a few seconds in both positive and negative ion modes. By investigating the mass spectral changes of asphalt fumes at different heating temperatures ranging from 50 to 200 °C, the temperature factor of asphalt fume emission was demonstrated in this work. The research results demonstrate that the complexity of asphalt fumes is positively related to the applied temperature. Moreover, the VOCs of saturates, aromatics, resins, and asphaltenes fractions were also analyzed by the direct analysis method. The result shows that aromatics contribute most to the emission of VOCs. In addition, the obtained mass spectra combined with the principal component analysis method show the great potential to quickly screen VOC inhibitors of asphalt materials.

13.
Front Immunol ; 14: 1237350, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575252

RESUMO

Background: Hepatocellular carcinoma (HCC) represents a prominent gastrointestinal malignancy with a grim clinical outlook. In this regard, the discovery of novel early biomarkers holds substantial promise for ameliorating HCC-associated mortality. Efferocytosis, a vital immunological process, assumes a central position in the elimination of apoptotic cells. However, comprehensive investigations exploring the role of efferocytosis-related genes (EFRGs) in HCC are sparse, and their regulatory influence on HCC immunotherapy and targeted drug interventions remain poorly understood. Methods: RNA sequencing data and clinical characteristics of HCC patients were acquired from the TCGA database. To identify prognostically significant genes in HCC, we performed the limma package and conducted univariate Cox regression analysis. Subsequently, machine learning algorithms were employed to identify hub genes. To assess the immunological landscape of different HCC subtypes, we employed the CIBERSORT algorithm. Furthermore, single-cell RNA sequencing (scRNA-seq) was utilized to investigate the expression levels of ERFGs in immune cells and to explore intercellular communication within HCC tissues. The migratory capacity of HCC cells was evaluated using CCK-8 assays, while drug sensitivity prediction reliability was determined through wound-healing assays. Results: We have successfully identified a set of nine genes, termed EFRGs, that hold significant potential for the establishment of a hepatocellular carcinoma-specific prognostic model. Furthermore, leveraging the individual risk scores derived from this model, we were able to stratify patients into two distinct risk groups, unveiling notable disparities in terms of immune infiltration patterns and response to immunotherapy. Notably, the model's capacity to accurately predict drug responses was substantiated through comprehensive experimental investigations, encompassing wound-healing assay, and CCK8 experiments conducted on the HepG2 and Huh7 cell lines. Conclusions: We constructed an EFRGs model that serves as valuable tools for prognostic assessment and decision-making support in the context of immunotherapy and chemotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Reprodutibilidade dos Testes , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Prognóstico , Análise de Célula Única
14.
J Phys Condens Matter ; 35(26)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36990099

RESUMO

Two-dimensional (2D) half-metal and topological states have been the current research focus in condensed matter physics. Herein, we report a novel 2D material named EuOBr monolayer, which can simultaneously show 2D half-metal and topological fermions. This material shows a metallic state in the spin-up channel but a large insulating gap of 4.38 eV in the spin-down channel. In the conducting spin channel, the EuOBr monolayer shows the coexistence of Weyl points and nodal-lines near the Fermi level. These nodal-lines are classified by type-I, hybrid, closed, and open nodal-lines. The symmetry analysis suggests these nodal-lines are protected by the mirror symmetry, which cannot be broken even spin-orbit coupling is included because the ground magnetization direction in the material is out-of-plane [001]. The topological fermions in the EuOBr monolayer are fully spin-polarized, which can be meaningful for future applications in topological spintronic nano-devices.

15.
Bioengineered ; 13(2): 2554-2567, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35156520

RESUMO

Warburg effect is considered to be related to the malignancy of tumor cells under hypoxic conditions, but the underlying mechanism remains unknown. In this article, it has been reported that lncRNA LINC00525 is a hypoxia-responsive lncRNA and is essential for hypoxia-enhanced glycolysis. It was found that LINC00525 was up-regulated, and promoted cell proliferation in colorectal cancer in vitro and in vivo. In colorectal cancer cells, hypoxia increasedLINC00525 expression, whereas knocking down LINC00525 reduced hypoxia-enhanced glycolysis. For specific molecular mechanisms, it was found that LINC00525 promoted UBE2Q1 expression by binding miR-338-3p, and UBE2Q1-stabilized ß-catenin enhances hypoxia-enhanced glycolysis by activating HIF-1α. In conclusion, these findings showed that LINC00525 was essential for hypoxia-enhanced glycolysis; its mechanism was related to activating HIF-1α through miR-338-3p/UBE2Q1/ß-catenin axis in colorectal cancer cells.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Nus , MicroRNAs/genética , RNA Longo não Codificante/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , beta Catenina/metabolismo
16.
Int J Mol Med ; 49(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34726250

RESUMO

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that certain of the flow cytometric data featured in Fig. 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 44: 1139­1150, 2019; DOI: 10.3892/ijmm.2019.4245].

17.
PeerJ ; 10: e14359, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420130

RESUMO

The ecological environment of quarry mining area is fragile, and the vegetation restoration cycle is long and difficult, so scientific and appropriate artificial vegetation is of great significance to ecological restoration. The purpose of this study was to evaluate the herbaceous and woody vegetation restoration, including Medicago sativa (Me), artificial miscellaneous grass (Mg), Rhus typhina (Rh), fruit orchard (Or) and Pinus tabulaeformis (Pi), to investigate the soil physicochemical properties and the structure of the microbial communities, and to reveal the correlation between them. The results addressed that Medicago sativa and artificial miscellaneous grass had significant effect on soil remediation, which were conducive to scientific and efficient ecological restoration, and could promote ecological restoration in the damaged ecosystems. While, the modes of Rh and Pi were not suitable for ecological restoration in this study area because they had strong allelopathy. Another arborous restoration mode of Or showed a better improvement effect (including soil nutrients, soil microbial diversity, etc.) than that of Rh and Pi. The findings also indicated that the herbaceous vegetation restoration modes of Me and Mg significantly increased the relative abundance of Proteobacteria, Acidobacteria, Actinobacteria bacteria, Ascomycota and Mortierllomycota fungi, and reduced the relative abundance of Firmicutes bacteria and Basidiomycota fungi. This study also revealed that the trend of bacterial localization in the fruit orchard, artificial miscellaneous grass and Medicago sativa was more obvious. Among many soil abiotic factors, the contents of organic matter, available nitrogen and pH were the most important factors affecting soil microbial community.


Assuntos
Ascomicetos , Microbiota , Solo/química , Bactérias , Proteobactérias , Poaceae
18.
Curr Pharm Biotechnol ; 23(14): 1637-1646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34514987

RESUMO

BACKGROUND: HSP90 has been considered an important anticancer target for several decades, but traditional HSP90 N-terminal inhibitors often suffered from organ toxicity and/or drug resistance. METHODS: The development of HSP90 C-terminal inhibitors represents a reliable alternative strategy. In view of rare examples of structure-based identification of HSP90 C-terminal inhibitors, we report a virtual screening based strategy for the discovery of HSP90 C-terminal inhibitors as anticancer agents from natural products. RESULTS & DISCUSSION: 13 chemical ingredients from licorice were identified as possible HSP90 inhibitors and 3 of them have been reported as anticancer agents. The binding modes towards HSP90 C-terminus were predicted by molecular docking and refined by molecular dynamics simulation. CONCLUSION: Further network pharmacological analysis predicted overall possible targets involved in the pathways in cancer and revealed that 8 molecules possibly interact with HSP90. A structure based virtual screening strategy was established for the discovery of HSP90 Cterminal inhibitors.


Assuntos
Antineoplásicos , Produtos Biológicos , Simulação de Acoplamento Molecular , Antineoplásicos/farmacologia , Proteínas de Choque Térmico HSP90 , Simulação de Dinâmica Molecular
19.
Mol Cancer Res ; 20(11): 1697-1708, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-35857351

RESUMO

Recently, long noncoding RNAs (lncRNA) have been reported as tumor suppressors or oncogenes in colorectal cancer. This study aims to discover functional role of a novel lncRNA in colorectal cancer tumorigenesis. Expression profile of fibronectin type III domain containing 1 antisense RNA 1 (ELFN1-AS1) in colorectal cancer samples was displayed on TCGA database. Expression level of ELFN1-AS1 was tested in colorectal cancer tissues and cell lines via qRT-PCR. Functional role of ELFN1-AS1 was assessed by loss-of-function assays. Mechanism experiments, such as chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay, were done to analyze the molecular mechanism of ELFN1-AS1 in colorectal cancer. ELFN1-AS1 knockdown inhibited colorectal cancer tumor growth through restricting cell proliferation and facilitating cell apoptosis. ELFN1-AS1 was transcriptionally activated by MYC. Moreover, ELFN1-AS1 led to transcriptional silencing of tropomyosin 1 (TPM1) via recruiting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and forkhead box P1 (FOXP1). Collectively, MYC-upregulated ELFN1-AS1 recruited EZH2 and FOXP1 to restrain TPM1 expression, thereby promoting colorectal cancer tumor growth. IMPLICATIONS: This study revealed a novel molecular pathway in colorectal cancer progression, which may provide new method for early diagnosis and treatment of colorectal cancer.


Assuntos
Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação para Cima , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , MicroRNAs/genética , Tropomiosina/genética , Tropomiosina/metabolismo , Proteínas Repressoras/genética , Fatores de Transcrição Forkhead/genética
20.
Poult Sci ; 101(2): 101306, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34942517

RESUMO

The objective of this experimental study was to examine the effects of the Chinese herbal medicines Patchouli and Elsholtzia on the follicular granulosa cells of hens undergoing heat stress conditions. In the current investigation, hen follicular granulosa cells were isolated from the prehierarchical follicles of layer hens and then cultured in-vitro. The cells were randomly divided into the 6 groups. Following the completion of this study's experiments using different heat stress and medicinal treatments, the cell activities of each group were measured using an MTT method. The levels of the heat shock protein 70 (HSP70) were detected using ELISA. The expressions of the steroidogenic acute regulatory protein (StAR) mRNA; cytochrome P450 family 11, subfamily A, member 1 (CYP11A1) mRNA; proliferating cell nuclear antigen (PCNA) mRNA; and the follicle stimulating hormone receptor (FSHR) were detected using the real-time quantitative polymerase chain reactions. The concentration levels of estrogen and progesterone in the cell supernatant of each group were measured using ELISA. The results showed that cell activity had significantly decreased following the heat stress treatments at 43℃, 44℃, and 45℃ (P < 0.01), respectively. Meanwhile, cell activities observed in Patchouli and Elsholtzia were found to be much better than those of heat stress group (P < 0.05). In addition, the expression levels of HSP70 in the follicular granulosa cells of Patchouli and Elsholtzia groups were lower than those of heat stress group. Patchouli and Elsholtzia can maintain expressions of the receptor at 43℃. This study determined that the estrogen and progesterone in the supernatant fluid of Patchouli and Elsholtzia were higher than those observed in heat stress. Therefore, the results obtained in this study indicated that the Patchouli and Elsholtzia treatments administered prior the heat stress experiments had successfully protected the follicular granulosa cells from heat damages while maintaining the normal secretory functions of the granulosa cells.


Assuntos
Galinhas , Pogostemon , Animais , Células Cultivadas , Feminino , Células da Granulosa , Resposta ao Choque Térmico , Progesterona
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